The mechanism of interferon induction in human fibroblast cells by synthetic polynucleotides has been studied in this laboratory for a number of years. It was shown that the induction is a fast process which, in cell systems used, was not limited by the stability of the inducer. The biological activity of poly IC complex depended more on the integrity of poly I than of poly C strand; but overall, the structural requirements for the triggering event were found less stringent than previously thought. When coupled to sephadex or cellulose particle, poly IC retained its biological activity; nevertheless, in all systems studied, some release of polynucleotide from the carrier was observed and, therefore, the experiments did not locate the triggering site unambiguously. By specific membrane treatment (such as Con A), it was possible to interrupt the antiviral effect of poly IC without modifying the recognition function of membrane receptors. Steps leading to interaction of poly IC with the "hypothetical" triggering site have been studied in more detail. Attempts to identify a specific membrane receptor(s) will be undertaken examining how they participate in the antiviral effects of poly IC. Furthermore, the mechanism of poly IC's entry into the cytoplasm and its relation to interferon induction has been examined. Simultaneously, post-triggering events in interferon induction have been examined on a molecular level. The purified interferon in mRNA will be translated, both in cell and cell-free systems. Kinetic studies of mRNAs and interferon production should help to determine whether the induction of interferon is limited by its mRNA or whether some post-transcriptional events are involed in the regulation of the cellular interferon levels. The highly radioactive interferon will be prepared and used for further studies on interferon mediated antiviral and cell growth inhibiting effects; furthermore, radioimmuno assay will be developed.